Intrinsic cardiac nerve activity and paroxysmal atrial tachyarrhythmia in ambulatory dogs.

Background: Little is known about the relationship between intrinsic cardiac nerve activity (ICNA) and spontaneous arrhythmias in ambulatory animals.

Methods And Results: We implanted radiotransmitters to record extrinsic cardiac nerve activity (ECNA; including stellate ganglion nerve activity and vagal nerve activity) and ICNA (including superior left ganglionated plexi nerve activity and ligament of Marshall nerve activity) in 6 ambulatory dogs. Intermittent rapid left atrial pacing was performed to induce paroxysmal atrial fibrillation or atrial tachycardia.

Electrophysiological characteristics of the Marshall bundle in humans.

Background: Marshall bundles (MBs) are the muscle bundles within the ligament of Marshall.

Objective: This trial sought to the electrophysiological characteristics of the MB and the anatomical connections between MB and left atrium (LA) in patients with persistent atrial fibrillation (AF).

Methods: We enrolled 72 patients (male:female 59:13, age 59.

The initiation of the heart beat.

During a normal lifetime, the heart may beat over 2 billion times, but the mechanisms by which the heart beats are initiated remain a subject of intense investigation. Since the discovery of a pacemaker current (I(f)) in 1978, multiple studies have shown that rhythmic changes in membrane voltage (the "membrane voltage clock") underlie the mechanisms of automaticity. The I(f) is a depolarization current activated during hyperpolarization.

The calcium and voltage clocks in sinoatrial node automaticity.

Recent evidence indicates that the voltage (cyclic activation and deactivation of membrane ion channels) and Ca(2+) clocks (rhythmic spontaneous sarcoplasmic reticulum Ca(2+) release) jointly regulate sinoatrial node (SAN) automaticity. Since the intact SAN is a heterogeneous structure that includes multiple different cell types interacting with each other, the relative importance of the voltage and Ca(2+) clocks for pacemaking may be variable in different regions of the SAN. Recently, we performed optical mapping in isolated and Langendorff-perfused canine right atria.

Ligament of Marshall: why it is important for atrial fibrillation ablation.

The ligament of Marshall (LOM) is located on the epicardium between the left atrial appendage and the left pulmonary veins. The corresponding endocardial structure is the left lateral ridge. LOM is a source of paroxysmal AF, and may activate at fast rates during persistent AF.

Diastolic intracellular calcium-membrane voltage coupling gain and postshock arrhythmias: role of purkinje fibers and triggered activity.

Rationale: Recurrent ventricular arrhythmias after initial successful defibrillation are associated with poor clinical outcome.

Objective: We tested the hypothesis that postshock arrhythmias occur because of spontaneous sarcoplasmic reticulum Ca release, delayed afterdepolarization (DAD), and triggered activity (TA) from tissues with high sensitivity of resting membrane voltage (V(m)) to elevated intracellular calcium (Ca(i)) (high diastolic Ca(i)-voltage coupling gains).

Methods And Results: We simultaneously mapped Ca(i) and V(m) on epicardial (n=14) or endocardial (n=14) surfaces of Langendorff-perfused rabbit ventricles.

Adipose stromal cells and platelet-rich plasma therapies synergistically increase revascularization during wound healing.

Background: The authors examined the efficacy of adipose stem cells, when supplied either alone or in platelet-rich fibrin gels, to improve wound healing.

Methods: A porcine full-thickness wound model was used to compare six topical treatments: platelet-poor plasma; platelet-rich plasma; autologous adipose stem cells plus platelet-poor plasma; autologous adipose stem cells plus platelet-rich plasma; allogeneic adipose stem cells containing green fluorescent protein plus platelet-poor plasma; and saline (control). One week after isolation, adipose stem cells were applied to full-thickness wounds on the paraspinal and thoracic regions of three pigs (44 wounds per pig; each treatment was applied to eight separate wounds).

Intracellular calcium dynamics and acceleration of sinus rhythm by beta-adrenergic stimulation.

Background: Recent evidence indicates that membrane voltage and Ca2+ clocks jointly regulate sinoatrial node (SAN) automaticity. Here we test the hypothesis that sinus rate acceleration by beta-adrenergic stimulation involves synergistic interactions between these clock mechanisms.

Methods And Results: We simultaneously mapped intracellular calcium (Ca(i)) and membrane potential in 25 isolated canine right atrium, using previously described criteria of the timing of late diastolic Ca(i) elevation (LDCAE) relative to the action potential upstroke to detect the Ca2+ clock.

The QT syndromes: long and short.

This Seminar presents the most recent information about the congenital long and short QT syndromes, emphasising the varied genotype-phenotype association in the ten different long QT syndromes and the five different short QT syndromes. Although uncommon, these syndromes serve as a Rosetta stone for the understanding of inherited ion-channel disorders leading to life-threatening cardiac arrhythmias. Ionic abnormal changes mainly affecting K(+), Na(+), or Ca(2+) currents, which either prolong or shorten ventricular repolarisation, can create a substrate of electrophysiological heterogeneity that predisposes to the development of ventricular tachyarrhythmias and sudden death.

Heart-brain interactions in cardiac arrhythmias: role of the autonomic nervous system.

The autonomic nervous system plays an important role in the genesis of ventricular arrhythmias and sudden cardiac death. Evidence is substantial for a neural component in sudden cardiac death. Sympathetic nerve sprouting and regional myocardial hyperinnervation following myocardial injury promote cardiac arrhythmia and sudden cardiac death through several potential mechanisms.

Stem cell differentiation: cardiac repair.

Cellular transplantation has been employed for several years to deliver donor cardiomyocytes to normal and injured hearts. Recent reports of a variety of stem cells with apparent cardiomyogenic potential have raised the possibility of cell transplantation-based therapeutic interventions for heart disease. Here we review the preclinical studies demonstrating that intracardiac transplantation of skeletal myoblasts, cardiomyocytes and cardiomyogenic stem cells is feasible.

Expression of a mutant p193/CUL7 molecule confers resistance to MG132- and etoposide-induced apoptosis independent of p53 or Parc binding.

p193/CUL7 is an E3 ubiquitin ligase initially identified as an SV40 Large T Antigen binding protein. Expression of a dominant interfering variant of mouse p193/CUL7 (designated 1152stop) conferred resistance to MG132- and etoposide-induced apoptosis in U2OS cells. Immune precipitation/Western analyses revealed that endogenous p193/CUL7 formed a complex with Parc (a recently identified parkin-like ubiquitin ligase) and p53.

Epidemiology and mechanisms of sudden cardiac death.

A particular challenge in preventing sudden cardiac death is our limited means of identifying individuals, rather than populations, at risk. Genetic and molecular risk factors are among the new measures currently being explored. Until effective risk recognition and stratification methods are available, general prevention--including cardioprotective therapies and the widespread availability of automatic external defibrillators--remains important.

Targeted expression of cyclin D2 results in cardiomyocyte DNA synthesis and infarct regression in transgenic mice.

Restriction point transit and commitment to a new round of cell division is regulated by the activity of cyclin-dependent kinase 4 and its obligate activating partners, the D-type cyclins. In this study, we examined the ability of D-type cyclins to promote cardiomyocyte cell cycle activity. Adult transgenic mice expressing cyclin D1, D2, or D3 under the regulation of the alpha cardiac myosin heavy chain promoter exhibited high rates of cardiomyocyte DNA synthesis under baseline conditions.

Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells.

Background: The delivery of autologous cells to increase angiogenesis is emerging as a treatment option for patients with cardiovascular disease but may be limited by the accessibility of sufficient cell numbers. The beneficial effects of delivered cells appear to be related to their pluripotency and ability to secrete growth factors. We examined nonadipocyte stromal cells from human subcutaneous fat as a novel source of therapeutic cells.

Increase in ventricular tachycardia frequency after biventricular implantable cardioverter defibrillator upgrade.

We report the case of a patient in whom transvenous left ventricular pacing lead placement at the time of a biventricular upgrade led to an exacerbation of clinical monomorphic ventricular tachycardia (MVT). At implant, slow left ventricular pacing repeatedly induced sustained MVT. However, testing of the biventricular pacing showed no MVT inducibility, and the system was implanted.

Congenital bicuspid aortic valve enodocarditis with multiple subvalvular complications and an acquired membranous ventricular septal defect.

We report a case with echocardiographic demonstration of native congenital bicuspid aortic valve endocarditis with multiple subaortic complications. Transesophageal echocardiography in this case revealed large vegetations with multiloculated aortic paravalvular abscess around the cusps; a high-acquired restrictive membranous ventricular septal defect with vegetations extending to the tricuspid leaflets and paravalvular aortic regurgitation caused by aortic leaflet perforation.

Atrial fibrillation: what are the targets for intervention?

Atrial fibrillation (AF) is a difficult and growing problem in the population. While medical therapy controls symptoms in many patients, a proportion of individuals with this common arrhythmia cannot be optimally managed with drugs alone. However, truly curative therapy for AF has always been one of the "holy grails" of electrophysiology.

Peripheral blood "endothelial progenitor cells" are derived from monocyte/macrophages and secrete angiogenic growth factors.

Background: Endothelial progenitor cells (EPCs) have been isolated from peripheral blood and can enhance angiogenesis after infusion into host animals. It is not known whether the proangiogenic effects are a result of such events as endothelial differentiation and subsequent proliferation of EPCs or secondary to secretion of angiogenic growth factors.

Methods And Results: Human EPCs were isolated as previously described, and their phenotypes were confirmed by uptake of acetylated LDL and binding of ulex-lectin.

Smooth muscle-specific expression of SV40 large TAg induces SMC proliferation causing adaptive arterial remodeling.

To study the effects of enhanced smooth muscle cell (SMC) proliferation on arterial vessel geometry in the absence of vessel trauma, we developed a transgenic mouse model expressing SV40 large T antigen under control of the 2.3-kb smooth muscle-myosin heavy chain promoter. Transgenic mice studied at ages from 3 to 13 wk showed a 3.